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Moduladores de los receptores de la esfingosina 1-fosfato en la esclerosis múltiple y otras enfermedades

Marisa P McGinley¹, Jeffrey A Cohen¹

¹Mellen Center, Cleveland Clinic, Cleveland, OH, USA.

Lancet (London, England)

|June 27, 2021

Resumen

Los moduladores de los receptores de esfingosina 1-fosfato (S1P) están aprobados para la esclerosis múltiple mediante la reducción de los linfocitos circulantes. Investigaciones adicionales apoyan su potencial para otras aplicaciones terapéuticas.

Área de la Ciencia:

Inmunología
Farmacología
La neurociencia

Sus antecedentes:

Las vías de señalización de Sphingosine 1-phosphate (S1P) regulan los procesos fisiológicos críticos.
Los receptores S1P (S1PR) están implicados en el tráfico de linfocitos, las respuestas inmunes y la función de los órganos.
Los S1PR son reconocidos como objetivos terapéuticos para diversas enfermedades.

Objetivo del estudio:

Revisar el papel de los moduladores S1PR en la esclerosis múltiple.
Explorar el potencial terapéutico de los moduladores S1PR más allá de la esclerosis múltiple.

Principales métodos:

Revisión de la literatura científica sobre los moduladores S1PR.
Análisis de datos preclínicos y resultados de ensayos clínicos.
Examen del mecanismo de acción de S1PR en la esclerosis múltiple.

Principales resultados:

Cuatro moduladores S1PR (fingolimod, siponimod, ozanimod, ponesimod) están aprobados para la esclerosis múltiple.
El mecanismo principal en la esclerosis múltiple implica la internalización de S1PR1 en los linfocitos, reduciendo la inflamación del SNC.
La evidencia preclínica y clínica sugiere aplicaciones terapéuticas más amplias.

Conclusiones:

Los moduladores S1PR representan un avance terapéutico significativo para la esclerosis múltiple.
Las diversas funciones de la señalización S1P indican un futuro prometedor para los moduladores S1PR en otras enfermedades.
La investigación en curso continúa expandiendo el panorama terapéutico para los moduladores S1PR.

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